Protein Kinase C-α is a Critical Protein for Antisense Oligonucleotide-mediated Silencing in Mammalian Cells

摘要: We have identified the existence of a productive, PKC-α-dependent endocytotic silencing pathway that leads gymnotically-delivered locked nucleic acid (LNA)-gapmer phosphorothioate antisense oligonucleotides (ASOs) into late endosomes. By blocking maturation early endosomes to endosomes, expression PKC-α results in potent reduction ASO ability cell. also demonstrated gene cytoplasm is vitiated when reduced. Restoring via reconstitution experiment reinstates ASOs silence. These advance our understanding intracellular trafficking and activity following gymnotic delivery, further demonstrate two distinct pathways mammalian cells, one cytoplasmic other nuclear compartment.